Efficacy and safety of regimens used for the treatment of multicentric Castleman disease: A systematic review.

OBJECTIVES: Treatment options for multicentric Castleman disease (MCD) remain limited. The only FDA-approved drug is siltuximab for idiopathic MCD (iMCD), but the response rate with siltuximab is less than 50%. We performed a systematic review to examine the efficacy and safety of various regimens used for the treatment of MCD. METHODS: A database search on PubMed, Embase, Cochrane, Web of Science, and Clinicaltrials.gov using the terms "Castleman disease," "treatment outcome," and "patient safety" was done. RESULTS AND CONCLUSIONS: Results from a randomized controlled trial and an extension study highlighted the efficacy and long-term safety of siltuximab for iMCD; other trials showed tocilizumab to be a suitable alternative. A recent trial reported high response rates with thalidomide in iMCD patients. Promising results were reported for bortezomib in relapsed/ refractory MCD. For human herpesvirus-8 (HHV8)-associated MCD, rituximab along with doxorubicin therapy followed by maintenance with zidovudine and valganciclovir is the most effective therapy. A single-arm trial has highlighted the potential role of tocilizumab in HHV8-MCD. Data for these regimens are limited and mostly comprise nonrandomized trials. Further research on emerging agents could have a major impact on the treatment of this rare disease.

Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP. METHODS: The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model. RESULTS: Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty). CONCLUSIONS: Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.

Left Ventricular Hypertrophy (LVH) and Left Ventricular Geometric Patterns in Patients with Chronic Kidney Disease (CKD) Stage 2-5 With Preserved Ejection Fraction (EF): A Systematic Review to Explore CKD Stage-wise LVH Patterns.

Left ventricular hypertrophy (LVH) is the most common structural abnormality associated with CKD patients accounting for 70% of the patients suffering LVH with ESRD. This art of the state review is first of its nature which aimed to analyze the studies involving LVH in CKD patients, and stage-wise association of CKD with various geometrical patterns of LVH. The literature search was done through various databases like PubMed, EMBASE, CINAHIL, Web of Science, and Cochrane Library. After careful quality assessment a total of 7 studies, and 2121 patients were included in our study. The mean age of the patients was 61.5±12.4 years. Similarly, the mean value of eGFR was 39.81±13.71 ml/min. The incidence of LVH was 47.05%, and on stage-wise analysis, the higher CKD stage was associated with eccentric LVH as compared to lower stages. The ejection fraction (EF) values were showing preserved EF in all included studies. ESRD was showing more preponderance towards eccentric LVH as compared to other stages of CKD.

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.

Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies. However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys. In this review, we summarized the available evidence on the safety profile of CAR T-cell therapy in patients with pre-existing renal insufficiency/AKI and in those who develop AKI as a result of CAR T-cell therapy. With a 30% incidence of AKI post-CAR T-cell, various pathophysiological mechanisms, such as CRS, hemophagocytic lymphohistiocytosis (HLH), TLS, serum cytokines, and inflammatory biomarkers, have been shown to play a role. However, CRS is commonly reported as an underlying mechanism. Overall, 18% of patients in our included studies developed AKI after receiving CAR T-cell therapy, and most cases were reversible with appropriate therapy. While phase-1 clinical trials exclude patients with significant renal toxicity, two studies (Mamlouk et al. and Hunter et al.) reported successful treatment of dialysis-dependent patients with refractory diffuse large B-cell lymphoma, and demonstrated that CAR T-cell therapy and lymphodepletion (Flu/Cy) can be safely administered.

Oxygen targets following cardiac arrest: A meta-analysis of randomized controlled trials.

Introduction: The appropriate oxygen target post-resuscitation in out-of-hospital cardiac arrest (OHCA) patients is uncertain. We sought to compare lower versus higher oxygen targets in patients following OHCA. Methods: We searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov until January 2023 to include all randomized controlled trials (RCTs) that evaluated conservative vs. liberal oxygen therapy in OHCA patients. Our primary outcome was all-cause mortality at 90 days while our secondary outcomes were the level of neuron-specific enolase (NSE) at 48 h, ICU length of stay (LOS), and favorable neurological outcome (the proportion of patients with Cerebral Performance Category scores of 1-2 at end of follow-up). We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). Results: Nine trials with 1971 patients were included in our review. There was no significant difference between the conservative and liberal oxygen target groups regarding the rate of all-cause mortality (RR 0.95, 95% CI: 0.80 to 1.13; I2 = 55%). There were no significant differences between the two groups when assessing favorable neurological outcome (RR 1.01, 95% CI: 0.92 to 1.10; I2 = 4%), NSE at 48 h (MD 0.04, 95% CI: -0.67 to 0.76; I2 = 0%), and ICU length of stay (MD -2.86 days, 95% CI: -8.00 to 2.29 days; I2 = 0%). Conclusions: Conservative oxygen therapy did not decrease mortality, improve neurologic recovery, or decrease ICU LOS as compared to a liberal oxygen regimen. Future large-scale RCTs comparing homogenous oxygen targets are needed to confirm these findings.

Impact of Earthquake on Cardiovascular Health: What Should Cardiovascular Healthcare Providers Anticipate After the Devastating Earthquakes in Turkey and Syria?

Natural disasters like earthquakes have direct and indirect association with major adverse cardiac events. They can impact cardiovascular health by multiple mechanisms not to mention their impact on cardiovascular care and services. Besides the humanitarian tragedy that calls attention globally, we as part of cardiovascular community are concerned with the short and long outcomes of those who survived the recent Turkey and Syria earthquake tragedy. Therefore, in this review, we aimed to draw attention of cardiovascular healthcare providers to the anticipated cardiovascular issues that may arise in survivors on short- and long-term postearthquakes to ensure proper screening and earlier management of this population. With the anticipated increase in natural disasters in future considering climate changes, geological factors, and human activities, the cardiovascular healthcare providers as part of medical community should be aware of the high rate of cardiovascular disease burden that can occur among survivors of earthquakes and other natural disasters, so, they should act accordingly in terms of preparedness measures, adequate response planning starting from services re-allocation to personnel training and enhancing access to medical and cardiac care in both acute and chronic contexts, not to mention screening and risk-stratifying the patients to optimize their management.

Pneumocystis jiroveci Pneumonia: A Review of Management in Human Immunodeficiency Virus (HIV) and Non-HIV Immunocompromised Patients.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in Pneumocystis jirovecii pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of Pneumocystis jirovecii pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for Pneumocystis jirovecii pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.

Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

Allogeneic hematopoietic stem cell transplant (HSCT) is indicated in pediatric patients with acute lymphoblastic leukemia (ALL) who have relapsed or are at a very high risk of relapse during first complete remission. Two types of myeloablative conditioning are employed before allogeneic HSCT: total body irradiation (TBI)-based regimens and chemotherapy (CHT) alone. This study compares the efficacy and safety of TBI-based regimens and CHT-based conditioning in pediatric, adolescent, and young adult patients with ALL (0-24 years old). TBI-based and CHT-conditioning regimens were evaluated in 4262 and 1367 patients, respectively, from 15 studies. Compared to CHT alone, TBI-based regimens were associated with better overall survival (OS), relative risk (RR) 1.21, better event-free survival (RR 1.34), and a reduced risk of relapse (RR 0.69). Both approaches had comparable risk of acute graft-versus-host disease (GVHD), grades 3 to 4 acute GVHD, chronic GVHD, and nonrelapse mortality (NRM). In the subgroup analysis for patients in first complete remission, TBI-based regimens and CHT alone had comparable OS and NRM. Our results demonstrate the superiority of TBI-based regimens compared to CHT alone in pediatric patients with ALL.

Awake Prone Positioning for Non-Intubated COVID-19 Patients with Acute Respiratory Failure: A Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. METHODS: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. RESULTS: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74-0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77-1.11; moderate certainty) and did not increase the risk of adverse events. CONCLUSIONS: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.

Hospital-based salient prevention and control measures to counteract the 2022 monkeypox outbreak.

Monkeypox (MPX) has been declared a public health emergency of international concern by the World Health Organization. As of November 4, 2022, 78,000 verified cases from 109 countries and territories, and 40 deaths have been reported due to MPX. The present article highlights salient hospital-based prevention and control measures to be adopted and their critical role to mitigate the ongoing MPX outbreaks and global public health emergency.

Efficacy of Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Catheter ablation (CA) has emerged as an effective therapy for AF. We conducted a meta-analysis to update the current clinical evidence on the efficacy of CA for AF in patients with HCM. We searched PubMed, Embase, Cochrane and Clinicaltrials.gov for interventional and observational studies assessing single and multiple procedure success rate of CA in HCM patients. Our meta-analysis included 25 studies involving 1817 patients. Success rate following single procedure was 40.4% (95% CI 33.1 to 48.0%) at latest follow-up. The pooled success rate following multiple procedures was 51.4% (95% CI 42.9% to 60.0%) at latest follow-up. In the subgroup analysis for AF subtype, TCA was more successful for paroxysmal AF compared to non-paroxysmal AF. For the subset of studies reporting drug-free success rate, single and multiple procedures had a success rate of 33.4% (95% CI 19.3 to 49.1%) and 51.8% (95% CI 41.3 to 62.2%) at latest follow-up, respectively. CA is a suitable option for AF in patients with HCM. Success rate is greater in paroxysmal AF, after multiple procedures and with antiarrhythmic drugs.

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical features associated with these complications, and how to prevent and treat them. We included four original studies for this focused review. All four agents (idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, belantamab mafodotin) have received FDA approval for adult RRMM patients. We went through the FDA access data packages of the approved agents to outline stepwise management of the complications for better patient outcomes.

Analysis of risk factors and prognostic factors of brain metastasis in gastric cancer: a surveillance, epidemiology and end-results database study.

Brain metastasis in gastric cancer (GC) patients is a rare phenomenon that is associated with adverse clinical outcomes and poor survival rates. We conducted a retrospective cohort study to investigate the incidence, risk factors and prognostic factors of brain metastasis in GC patients. Data on sociodemographic and tumor characteristics of GC patients from 2010 to 2019 was extracted from the Surveillance, Epidemiology and End-Results (SEER) database. Descriptive statistics, multivariable logistic and Cox regression were applied on SPSS. Kaplan-Meier-Survival curves and ROC curves were constructed. A total of 59,231 GC patients, aged 66.65 ± 13.410 years were included. Brain metastasis was reported in 368 (0.62%) patients. On logistic regression, the risk of brain metastasis was significantly greater in males, patients aged < 60 years and patients having concurrent bone and lung metastasis. High grade and high N stage were significant risk factors for development of brain metastasis. Patients who had undergone surgery for the primary tumor were at reduced risk for brain metastasis (adjusted odds ratio 0.210, 95% CI 0.131-0.337). The median OS was 3 months in patients with brain metastasis and 17 months in patients without brain metastasis (p < 0.05). On Cox regression, Grade IV tumors and primary antral tumors were significant predictable parameters for poor prognosis. Overall Survival (OS) and Cancer-Specific Survival (CSS) were prolonged in patients who had undergone surgery. Brain metastasis in gastric cancer is associated with significantly worse survival. Employing large-scale screening for high-risk patients holds a promising impact to improve survival rates, but it must be accurately balanced with a comprehensive understanding of clinicopathological aspects for accurate diagnosis and treatment.

The Role of Bispecific Antibodies in Relapsed Refractory Multiple Myeloma: A Systematic Review.

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19-63%, and VGPR in 21-65%. The common adverse events were cytokine release syndrome (17-82%), anemia (5-52%), neutropenia (12-75%), and thrombocytopenia (14-42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response.

Assessment of health-related behaviors among medical students: A cross-sectional study.

Background and Aim: Students sometimes participate in harmful activities that adversely influence their behaviors and well-being throughout college, which is one of the sensitive phases in an individual's life. Aim: To assess the health-related behaviors of university students. Methods: A cross-sectional study that includes systematic randomly selected 383 students from various colleges of Ras Al Khaimah Medical and Health Sciences University (RAKMHSU), Ras Al Khaimah Emirate, United Arab Emirates. A self-reported questionnaire included students' demographic traits and behaviors, including safety, medication intake, cigarette smoking, nutrition, physical activity, and health-related topics. Results: Most participants were females (69.7%), 13.3% were obese while 28.2% were overweight. The data revealed a significant difference between male and female students regarding medication intake without prescription, nutrition, physical activity, and health-related topics. The data also revealed that the majority of the students were attempting to lose weight, and the former male smokers had fewer trials to quit the use of all tobacco products than females. Conclusion: More than a quarter of participants were overweight, and the majority of students did not adhere to the guidelines for safety and nutritious eating. This study recognized significant health promotion opportunities for university students that can be carried out to establish a healthier youth for society.

Adequacy of nitisinone for the management of alkaptonuria.

Alkaptonuria is a rare hereditary disease with a defective enzyme that results in increased homogentisic acid levels in the body. Homogentisic acid accumulates in multiple body parts and initializes tissue damage. Clinical manifestations such as pigmentation of the skin areas and joint destruction result in ochronosis. Nitisinone decreases serum and urinary homogentisic acid levels, improving morbidity by preventing and slowing the progression of alkaptonuria. Nitisinone-induced hypertyrosinemia causes keratopathy and mental ill effects, which can be managed by diet restriction and regular check-ups. A personalized approach is required for treatment by nitisinone. Low-dose oral nitisinone is associated with overall good results and a better safety profile.

Poliomyelitis in Pakistan: Challenges to polio eradication and future prospects.

Poliomyelitis is a viral disease that causes acute paralysis, muscle weakness and autonomic dysfunction. It primarily affects children under the age of five. It is mainly transmitted via the feco-oral route, through contaminated water. As of the year 2022, Pakistan remains one of the two countries where polio is still endemic, the other being Afghanistan. Numerous myths and misconceptions regarding the polio vaccine, lack of awareness and proper governance, terrorism and difficult access to remote areas due to poor infrastructure are just some of the reasons why polio remains endemic in Pakistan to this day. Therefore, the government should take measures to ensure the safety and wellbeing of health care workers, as well as spread awareness regarding the importance of polio vaccines, while addressing the myths and misconception regarding said vaccines.

Pattern of neurosurgical cases and procedures in Gilgit Baltistan: two-year experience at a newly established neurosurgical department.

BACKGROUND: In Pakistan, there are a total of 160 neurosurgeons that constitute a ratio of one neurosurgeon for a 5.5 million population. Gilgit Baltistan being a backward region does not have a single tertiary care facility. A new department of neurosurgery was established at Regional Headquarter City Hospital (RHQ) Gilgit with only one neurosurgeon. This study aimed to determine which neurosurgical diagnoses are common and which surgical interventions were performed at RHQ. METHODS: This is a retrospective cross-sectional study conducted at Regional Headquarter Hospital (RHQ) Gilgit in which data of patients operated for neurosurgical diseases between January 2020 and January 2022 was collected from patient record books. RESULTS: Of the total of 223 patients, 148 (66.3%) were males and 75 (33.6%) were females. A total of 92(41.2%) belonged to the pediatric age group. The top most diagnosis included Neurotrauma (46.6%), NTDs (13.9%) and CSDH (10.3%) while the most routinely performed procedures were craniotomy & hematoma evacuation (22.9%), debridement & elevation of DSF (20.6%), and burrhole evacuation (13.9%). In the pediatric age group, the top diagnosis was Neurotrauma (43.5%), NTDs (32.6%), and Hydrocephalus (19.6%) while in adults, neurotrauma (48.9%) was the leading diagnosis followed by CSDH (17.6%). In the pediatric age group, repair of NTDs (32.6%) was the most frequently performed procedure. CONCLUSION: This study shows different kinds of neurosurgical cases but because of a lack of diagnostic and therapeutic facilities, very limited operations were performed and many cases were referred to metropolitan cities. The hospitals in the region need further up-gradation to cater to the presenting burden.